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Carbon catabolite repression enables fungi to utilize the most favourable carbon source in the environment, and is mediated by a key regulator, CreA, in most fungi. CreA-mediated regulation has mainly been studied at high monosaccharide concentrations, an uncommon situation in most natural biotopes. In nature, many fungi rely on plant biomass as their major carbon source by producing enzymes to degrade plant cell wall polysaccharides into metabolizable sugars. To determine the role of CreA when fungi grow in more natural conditions and in particular with respect to degradation and conversion of plant cell walls, we compared transcriptomes of a creA deletion and reference strain of the ascomycete Aspergillus niger during growth on sugar beet pulp and wheat bran. Transcriptomics, extracellular sugar concentrations and growth profiling of A. niger on a variety of carbon sources, revealed that also under conditions with low concentrations of free monosaccharides, CreA has a major effect on gene expression in a strong time and substrate composition dependent manner. In addition, we compared the CreA regulon from five fungi during their growth on crude plant biomass or cellulose. It showed that CreA commonly regulated genes related to carbon metabolism, sugar transport and plant cell wall degrading enzymes across different species. We therefore conclude that CreA has a crucial role for fungi also in adapting to low sugar concentrations as occurring in their natural biotopes, which is supported by the presence of CreA orthologs in nearly all fungi.

Summary: The emergence of influenza A viruses (IAVs) from zoonotic reservoirs poses a great threat to human health. As seasonal vaccines are ineffective against zoonotic strains, and newly transmitted viruses can quickly acquire drug resistance, there remains a need for host-directed therapeutics against IAVs. Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung epithelial cells with a human isolate of an avian H5N1 strain. Several genes involved in sialic acid biosynthesis and related glycosylation pathways were highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter essential for IAV receptor expression and thus viral entry. Importantly, we have identified capicua (CIC) as a negative regulator of cell-intrinsic immunity, as loss of CIC resulted in heightened antiviral responses and restricted replication of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critical for the replication of intracellular pathogens. : Using a genome-wide CRISPR/Cas9 screen, Han et al. demonstrate that the major hit, the sialic acid transporter SLC35A1, is an essential host factor for IAV entry. In addition, they identify the DNA-binding transcriptional repressor CIC as a negative regulator of cell-intrinsic immunity. Keywords: CRISPR/Cas9 screen, GeCKO, influenza virus, host factors, sialic acid pathway, SLC35A1, Capicua, CIC, cell-intrinsic immunity, H5N1

The mainstay treatment of Clostridium difficile infections (CDI) is antimicrobials with growing support for fecal microbiota transplants. We report the first case of an elderly man with severe refractory NAP-1 pseudomembranous CDI who failed all medical therapy and two fecal transplants with response only seen after administration of intravenous immunoglobulin.

Conjoined twinning occurs in 1 in 100 sets of monozygotic twins, 1 in 50,000 gestations or 1 in 250,000 live births. With the advent of ultrasound technology, prenatal diagnosis of conjoined twins is possible. This article provides a comprehensive review of conjoined twins detected in the first trimester including fetal gender, maternal age, parity, types of fusion, related ultrasound abnormalities, perinatal outcome and association with assisted reproduction.

Conjoined twinning occurs in 1 in 100 sets of monozygotic twins, 1 in 50,000 gestations or 1 in 250,000 live births. With the advent of ultrasound technology, prenatal diagnosis of conjoined twins is possible. This article provides a comprehensive review of conjoined twins detected in the first trimester including fetal gender, maternal age, parity, types of fusion, related ultrasound abnormalities, perinatal outcome and association with assisted reproduction., (Copyright © 2011. Published by Elsevier B.V.)